This application represents a program project which will support 9 investigators who will work in various team combinations on problems relating to pulmonary disease and host defense reactions in the lung. The 8 projects have natural categorical groupings as follows: 1) Pathobiologic Mechanisms and Lung Diease (Acton, McCall, Myrvik, Kreger and Leake), 2) Etiologic, Immunologic and Genetic Studies on Sarcoidoiss (McLean, Leake, Kreger, Heise and Myrvik), 3) Host defense and Immunobiologic Responses in the Lung. In the first category, emphasis will be placed on the roles of delayed hypersensitivity mediators, host originated (endogenous) hydrolases and proteases of Serratia and Pseudomonas; complement dependent neutrophil sequestration and mechanisms of tissue injury in the lung following administration of bacterial LPS, inulin and immune complexes will be studied. In addition, a low molecular weight component released from the complement sequence by Cobra venom will be investigated. The second category of projects will emphasize preparation of Kveim active material, establishment of a sarcoid registry and studies on the etiologic, immunologic and genetic aspects of sarcoidosis. Ultrastructural studies will be a dominant activity in both of the above categorical groups. The third category will be concerned with animal models for studying the response of the lung to antigenic stimulation. Emphasis will be placed on cell-mediated and immunoglobulin responses; in addition, bacterial pneumonitis models will be developed. Plans also call for a study of pulmonary cells and the immunoglobulin content of lung wash fluids obtained from selected patients employing the broncholavage technique.